Social relationships and their associations with affective symptoms of women with breast cancer: A scoping review

Background Problems in affective and cognitive functioning are among the most common concurrent symptoms that breast cancer patients report. Social relationships may provide some explanations of the clinical variability in affective-cognitive symptoms. Evidence suggests that social relationships (functional and structural aspects) can be associated with patients’ affective-cognitive symptoms; however, such an association has not been well studied in the context of breast cancer. Purpose The purpose of this scoping review was to address the following question: What social relationships are associated with affective-cognitive symptoms of women with breast cancer? Methods This scoping review used the framework proposed by Arksey and O’Malley and PRISMA-Sc. Studies published by February 2022 were searched using four databases: MEDLINE (PubMed), Embase (Elsevier), PsycINFO (EBSCOhost), and Web of Science (Clarivate). All retrieved citations were independently screened and eligibility for inclusion was determined by study team members. Extracted data included research aims, design, sample, type and measures of social relationships (functional and structural), and the association between social relationships and affective-cognitive symptoms Results A total of 70 studies were included. Affective symptoms were positively associated with social support, family functioning, quality of relationships, social networks, and social integration, whereas the negative association was found with social constraints. Conclusion Our findings suggest positive social relationships may mitigate affective symptoms of women with breast cancer. Thus, health care providers need to educate patients about the importance of building solid social relationships and encourage them to participate in a supportive network of friends and family members.


Introduction
With advances in medical treatments, breast cancer mortality rates have steadily declined in recent years, resulting in an increase in 5-year survival rates [1]. According to the report from American Cancer Society in 2017, the overall survival rates have increased from 68% to 89% for White women and from 55% to 81% for Black women [2]. Resultantly, cancer is no longer viewed as an incurable acute disease. Instead, it follows the trajectories of chronic diseases that is characterized by periods of remission and exacerbation of symptoms [3]. Women with breast cancer often experience symptoms that co-occur (i.e., symptom clusters) during the disease trajectory [3]. For example, patients experience affective and cognitive problems (symptoms) concurrently. The co-occurrence of these symptoms is called a psychoneurological symptom cluster [4]. Further, these two symptoms within a psychoneurological cluster are strongly related to each other [4,5].
Problems in affective and cognitive functioning are among the most common concurrent symptoms that breast cancer patients report [4,5]. Affective symptoms include any mood disturbances that occur throughout the illness trajectory of cancer (e.g., depression, stress, anxiety, and fear), and such symptoms confers the risk of development of problems in memory, concentration, processing speed, and language (i.e., cognitive symptoms) [4,5]. Severe affective-cognitive symptoms may result in poor adherence of cancer treatments [6] and lower levels of functioning status and quality of life [7]. For this reason, it is critical to identify who may be at risk for affective as well as cognitive symptoms.
Factors that contribute to affective-cognitive (i.e., psychoneurological) symptoms were identified as stress, hypothalamic-pituitary-adrenocortical axis dysfunction, cytokine dysregulation, telomere shortening, or DNA damage [4]; however, these factors do not sufficiently explain the variability in these symptoms. For example, some patients have reported persistent and high levels of mood disturbance and cognitive impairment for several years or more following cancer treatment [8]. This finding suggests a need to investigate other potential factors that can explain their clinical variabilities.
Social relationships may provide some explanations of the clinical variability in affectivecognitive symptoms. Social relationships refer to the connections between individuals that they perceive to have personal meaning [9]. These relationships can be characterized as aspects, structural and functional. The structural aspect reflects the size, scope, and connectedness of social relations (e.g., social integration, social network), while the functional aspect covers the interpersonal interaction within the structure of the social relations (e.g., social support, family cohesion) [9]. Although the exact underlying mechanism of the association between social relationships and affective-cognitive symptoms remains unknown, several studies have examined this association. Recent systematic reviews have reported that the older populations showed a greater decline in their cognition when their social relationship was functionally and structurally poor [10,11]. Other studies have found that patients who had greater social support and cohesive relationships with their family members showed fewer depressive symptoms [12,13]. Specifically, breast cancer survivors demonstrated higher levels of depressive symptoms over the trajectory of their illness when they received lower levels of social support [14].
Taken together, greater social relationships (both functional and structural aspects) appear to be associated with fewer affective-cognitive symptoms in breast cancer patients. However, there is no comprehensive understanding on whether or which social relationships characteristics relate to BC patients' affective-cognitive symptoms. Therefore, the understanding of social relationship characteristics associated with affective-cognitive symptom in breast cancer patients may be important to as a basis for development of prevention and interventions to manage those symptoms.

Purpose
The purpose of this scoping review was to map the literature that has investigated both aspects of social relationships (functional and structural) and their links to affective-cognitive symptoms in breast cancer patients. This review paper addresses the following question: What social relationships are associated with affective-cognitive symptoms of women with breast cancer? This will lay the foundation for studies that explicate the mechanism of affective-cognitive symptoms in breast cancer patients. This understanding will also allow clinicians to identify patients more precisely at risk for affective-cognitive symptoms associated with social relationships and will contribute to the development of strategies to prevent and manage these symptoms.

Materials and methods
We reported the findings using the five methodological stages of scoping review developed by Arksey and O'Malley [15]. This review was conducted based on the following stages: 1) identifying the research question, 2) identifying relevant studies, 3) selecting studies, 4) charting the data, and 5) collating, summarizing, and reporting the results. A scoping review approaches was used because it helps clarify key concept related to outcomes as well as identify the types of available evidence [16]. We reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) [17].

Stage 1. Identifying research questions
We applied the PCO model to develop our research question [15]: "What social relationships ("C", concept) are associated with affective-cognitive symptoms ("O", outcome) of women with breast cancer ("P", population)?" We limited our study population of women with breast cancer aged 18 years and above because of different trajectories and manifestations of cognitive symptoms that children with cancer show compared with adults [18]. Table 1 describes eligibility criteria for the studies that were included in this scoping review.

Stage 2. Identifying relevant studies
We developed relevant search terms in collaboration with a librarian included a mix of keywords and database specific subject headings representing women, breast cancer, affective symptoms and social relationships. The search was translated and conducted by a medical research librarian on February 15, 2022 using four databases: MEDLINE (PubMed), Embase (Elsevier), PsycINFO (EBSCOhost), and Web of Science (Clarivate). Editorials, letters, and comments were excluded, as were animal-only studies and studies involving pediatric populations. Reproducible search strategies for all databases can be found in S1 Table. We reviewed the results for existing review articles and determined that no review articles currently exist on our topic.

Stage 3. Study selection
The search identified a total of 5,386 references that were imported into Covidence, a systematic review screening tool (Covidence systematic review software, Veritas Health Innovation, Melbourne, Australia. Available at www.covidence.org). Duplicate citations (n = 1,504) were automatically identified and removed by Covidence. The software ensures that two reviewers independently screened a total of 3,882 references by title and abstract. Studies were excluded if they did not clearly meet inclusion criteria, and of those, 3,723 references were deemed irrelevant and excluded. Upon the completion of screening titles and abstracts, any disagreements were resolved by discussion. One hundred fifty-nine citations were identified for full text assessment. At the full text review stage, articles were independently read by two different members of team (YY, YL, GS). During the full-text review, each study was reviewed independently to determine the final sample. Full-text studies that did not meet the inclusion criteria were excluded, and the reasons for exclusion were noted. Disagreement between the team members were resolved through discussion. Seventy articles were confirmed to be included in the final set for data extraction.

Stage 4. Charting the data
Our team developed a data extraction tool and determined which data should be extracted from studies to answer the research question. Two team members (YY, GS) independently piloted data abstraction from the first fifteen included studies using the data charting form. Then, they discussed the process and their results to confirm whether their approaches to data extraction were consistent. Questions arising when piloting the extract data form were discussed with the other team members (YL, TN). After piloting the form, two team members (YY, GS) independently recorded the following data from selected studies on the data charting form: 1) authors, 2) country of study, 3) year of publication, 4) study design, 5) sample characteristics (sample size, age, and type of cancer treatment), 6) type of social relationships 7) affective-cognitive symptoms and measurements, and 8) key findings (the association between social relationships and affective-cognitive symptoms).

Stage 5. Collating, summarizing and reporting the results
Our team collated, summarized, and reported all data obtained in stage 4 to map the knowledge on social relationships associated with affective-cognitive symptoms of adult women with breast cancer. The studies in the final sample were tabulated based on social relationships (e.g., functional or structural aspect of social relations). A table for the final sample was created and included the information on authors, years of publication, country of study, study population, type of social relationships, measures of affective-cognitive symptoms, and the association between social relationships and affective-cognitive symptoms. Verification of data accuracy was impudently conducted by six research team members (YY, YL, GS, SM, NC, JZ).

Association between social relationships and affective symptoms
In this review, social relationships were classified as functional and structural aspects of social relations. Of the included 70 studies, 64 focused on functional aspects of social relationships, and the remaining 6 reported on structural aspects of social relationships. Interestingly, none of the included 70 studies examined the association between social relationships and cognitive symptoms of breast cancer patients; thus, in this paper, we focused only on the affective symptoms of breast cancer patients and their association with patients' social relationships (Table 3).

Functional aspects of social relationships
Social support, satisfaction of social support, quality of the relationship, social constraints, and family functioning (including family conflict and family stress) are functional social relationships included in this review. Social support. Fifty-three studies examined the association between social support and affective symptoms among breast cancer patients. Of those 53 studies, four did not find any associations of affective symptoms with social support [21-24], whereas one showed that patients' affective symptoms can be changed depending on the source of provided support was   . Among 49 studies that reported significant association with affective symptoms, 37 investigated the association of patients' affective symptoms with the quantity of social support that patients received. The quantity of social support refers to the amount of social support that is available to patients (e.g., frequency of meetings) [25]. Patients showed lower levels of anxiety, depression, worry, mood disturbances, and psychological/mental distress when they received a greater quantity of social support [14,20,24,. Furthermore, some studies reported that the quantity of social support can predict the levels of patients' affective symptoms including their emotional well-being [51][52][53][54][55][56][57][58].
In addition to the quantity of social support, seven studies reported an association between type of social support and affective symptoms. Emotional (i.e., subjective) support, defined as support that includes the provision of care, empathy, and trust, was found to be most helpful to decrease patients' depression and anxiety. [37,47,56,59,60] In other words, as patients    Depression (PHQ-9) NR 1) Increased depression was associated with satisfaction with family/peer support (β = -0.42, p<0.01).
2) Decreases in social support quantity (β = -0.20) predicted increases in stress.     Anxiety (PANAS, SF received stronger emotional/subjective support, their experience of affective symptoms decreased. Some longitudinal studies showed that emotional/subjective support can function as a predictor of patients' anxiety and depression [34, 61,62]. Additionally, improvements in affective symptoms occurred when tangible support such as material support/assistance (e.g., brochures) was provided [34,37,56,59,61]. In six studies, patients' affective symptoms were affected by source and satisfaction of social support received. When patients received support from their family members, including a spouse or children, they reported less anxiety and depression [19,42,[63][64][65]. However, one study showed less depression and anxiety when support was received from friends compared to support from family [66]. In addition, higher satisfaction with support received was associated with the lower levels of patients' anxiety and depression [32,63,[67][68][69][70]. A study reported that patients showed less affective symptoms when they were more satisfied with support from family than from friends [66]. Patients' affective symptoms were not related to whether they were satisfied with their friend's support but were related to the amount of support received from a friend. Social support and/or social constraints. Three studies have examined the association of patients' depression with social constraints [71][72][73]. Patients who perceived social constraints from family (including spouse/partners) or friends showed higher depressive symptoms. However, patients showed lower depression when they had decreased family/friend social constraints. Patients reported no change in depression when social constraints increased [72,73]. Also, lower depression was reported when patients received greater social support.  Social support and family functioning. One study found that both patients' anxiety and depression decreased when they had greater social support and a better-functioning family [74]. Furthermore, family functioning predicted the levels of patients' anxiety and depression [74]. In line with this finding, three other studies also found higher depression in patients when they perceived poor/ineffective family functioning. Specifically, depression greatly increased when patients experienced inappropriate responses from family [75], conflicts between its members (i.e., family conflict) [76], and stress due to the demands on the family (i.e., family stress) [77].
Quality of relationships. Four studies investigated the quality of relationships with patients' partners/spouses that patients perceived and assessed its association with their affective symptoms. Of those four, two of them failed to show any significant associations of affective symptoms with the quality of couple/marital relationships [78,79]. However, one study showed that anxiety was not associated with patient's reported relationship quality but with the partner's reported relationship quality [79]. The other two studies showed that patients' psychological distress and mood disturbance increased when patients reported unsatisfying relationships with their spouse/partners [80,81]. Specifically, one study found that lower mood disturbance was reported when patients have a partner relationship with greater cohesion and expression (i.e., open communication) as well as more constructive conflicts [81]. The authors interpreted constructive conflicts as an indicator of greater engagement in the relationship with partners. In other words, constructive conflicts can occur due to greater discussion/understanding of each other's specific needs, and this constructive conflict can help reduce patients' mood disturbances.

Structural aspects of social relationships
Structural aspects of social relationships refers to the structure of social networks, such as the size and the linkage between members within a social network [9]. This review included social integration as the structural social relationships (Table 3).
Social integration. In this review, one RCT that investigated the effect of psychoeducational intervention examined the association between social integration and affective symptoms of breast cancer patients [82]. Social integration did not show any associations with the presence of psychiatric illness. However, one year after psychoeducational intervention, patients showed overall less depression when they perceived adequacy of both close relationships and more distant social ties (i.e., greater social integration).

Both aspects of social relationships
Social networks. Social networks can be assessed through whether individuals have important persons in their lives, type (e.g., friends or family) and duration of the relationship, and the frequency of contact with that persons [83]. Five studies assessed both of social networks and social support and their associations with patients' affective symptoms. Patients showed less anxiety and depression when they had stronger social support and social network (i.e., lower social isolation) [84][85][86][87][88]. Specifically, one longitudinal study showed that patients' depression at both initial and follow-up appointments was improved when they had a support person [84]. Another study also reported that living alone (without having a support person) contributed to increased anxiety as well as depression levels [86,88].

Discussion
Seventy studies met the inclusion criteria and informed this review. None of the included studies examined the association of social relationships with patients' cognitive symptoms, thus including studies that investigated the association of social relationships with affective symptoms. Of those 70 studies, four studies completely failed to show significant associations of affective symptoms with any aspects of social relationships [22-24, 78]; we found that most patients who participated in those four studies were primarily treated with surgery, which could be interpreted as showing very early stage breast cancer. However, in patients with advanced cancer (metastatic disease), better social relationships are associated with lower levels of their affective symptoms [19,20,67,81]. This finding suggests that patients with advanced stage cancer can benefit from social relationships in managing their affective symptoms compared with those with early stages of cancer. This review found that the level of social support and its association with affective symptoms change throughout the cancer treatment trajectory. Patients reported a decrease in social support before and after cancer treatments [14,61]. Specifically, a continuous decrease in emotional support was found after surgery for breast cancer, whereas informational or tangible support increased right after surgery and then dropped over time [34,63]. Although the overall levels of social support showed a decreased trend, the magnitude of its association with affective symptoms increased over time [14,29,61]. These findings suggest the need to assess the level of social support and implement programs to optimize social support, especially for those at the end of cancer treatments.
We further found several factors that help explain the link between social support and affective symptoms. A study showed that women with higher social support appraised their illness as less stressful situations and, in turn, fewer mood disturbances [61]. Another study also found that patients who perceived lower level of social support tend to choose passive coping strategy (i.e., self-blame) rather than active coping (i.e., positive reframing), which in turn decrease emotional well-being [54]. In contrast, those who received higher level of social support are more likely to rely on active coping, resulting in enhancing emotional well-being [54]. Similarly, Hills and colleagues (2011) reported higher self-blame and lower social support predict greater levels of depression and anxiety [55]. In addition to the appraisal of illness and coping strategies, several other studies showed that demographic information (age, income, education, marital status), clinical information (cancer stage, type of surgery, treatment types), physical function, and coping styles have comparable effects to social support on mood disturbances [37,77]. Further studies are needed to identify factors that explain the link between social support and affective symptoms; doing so will help develop targeted interventions.
In this review, social relationships were divided into their function and structural aspects. Functional aspects of social relationships include four variables: social support, social constraints, family functioning, and quality of relationship. Social support refers to aid provided (e.g., emotional or instrumental) through contact with one's social networks (e.g., friends or family) [9,49,83], whereas social constraints are social conditions that hinder individuals' expression of stressors due to unsupportive, misunderstood, or isolated responses from others [89]. Our findings clearly show that patients' affective symptoms are positively associated with the quantity (e.g., time spent or availability), type (e.g., tangible aid or empathy), source (i.e., who provided support), and satisfaction from the support that they received. Additionally, greater levels of affective symptoms are associated with negative social interactions (i.e., social constraints) and poor family functioning.
Compared with three functional aspects above, findings regarding the quality of social relationships are not consistent. Some studies reported that the quality of relationships is associated with patients' affective symptoms [80,81], but others do not [78,79]. Furthermore, one study showed that patients who reported greater conflicts in relationships with partners also reported lower mood disturbances [81].This inconsistency can occur due to differences in sample characteristics. For example, patients included in Giese-Davis and Hermanson (2000)'s study reported more metastatic diseases compared to those of other three studies [78][79][80]. In addition, the study conducted by Al-Zaben and colleagues (2015) included married couples and investigated their marital quality, whereas other three studies focused on the relationship quality/satisfaction with their significant others. Future studies would benefit from ensuring consistency and specificity in defining and measuring quality of social relationships.
Similarly, structural aspects of social relationships also show an association with patients' affective symptoms. All six included studies showed that having a support person, not living alone, and building close relationships with others are factors that lower patients' affective symptoms. It is possible that patients with larger social networks and greater social integration may increase the odds that patients will have friends and family who survive as peer and familiar support [90]. This support can be beneficial while patients are managing symptoms from disease and/or treatment [90]. Additional research is needed to understand how structural and functional aspects of social relationships interact with biological factors (e.g., cytokines, HPA axis dysfunction) to influence patients' affective symptoms. This understanding may help identify important concepts for models that promote social relationships in breast cancer patients that will help improve their affective symptoms.

Implication for practice
Most interventions for those with affective symptoms have primarily focused on managing their internal clinical characteristics. However, our findings reveal that positive social relationships benefit in mitigating affective symptoms of women with breast cancer. Thus, healthcare providers need to educate patients about the importance of building positive social relationships and encourage them to participate in a supportive network of friends and family members. Specifically, patients with advanced cancer (i.e., metastatic status) may find it highly beneficial to have access to support groups that are relevant to their specific needs. For example, health professionals can encourage them to participate in interventions that include components such as communication skills training or coordinating coping responses; in turn, this will help improve the quality of relationships.
Based on findings from this review paper, there is a need to capitalize on existing relationships that patients perceive as beneficial in their everyday lives like those considered as family members. Family intervention development that aims to lower affective symptoms as well as improve quality of life and well-being may be a suitable next step in improving patient outcomes. For example, family-based group tasks that improve family functioning or family conflicts can be provided to breast cancer patients and their family members as a part of the intervention for improving affective-cognitive symptoms.
Lastly, it is important in the clinical setting to assess social support and social constraints. This type of assessment may be helpful in preventing, and furthermore, mitigating their affective symptoms. Assessment tools for social relationships including social support or social constraints can be built into the medical chart to alert for clinical staff to address. Additionally, establishing a social system to support coordination of various types of social relationships from healthcare professionals may yield positive affective outcomes in breast cancer patients. While evidence supporting this association is limited, more studies on the impact of social relationships on affective symptoms of breast cancer patients are recommended.

Limitations
Our study goal was to find literature that examined the association between social relationships and cognitive symptoms among breast cancer patients. The review of literature yielded that there are no published studies that study this association based on our review criteria. During the literature search, we found several studies that investigated this association in healthy older adults [10,11]. However, no studies have been conducted in the context of breast cancer. We only included articles that explore the association between social relationships and affective symptoms of breast cancer patients. Future research that considers the effect of social relationships on cognitive symptoms in breast cancer is needed to advance our knowledge in cancer symptom science.
Approximately half of the included studies did not report confounding factors (e.g., sociodemographic) and did not adjust for these factors. This is an important limitation because the associations between social relationships and a patients' affective symptoms could differ depending on confounding factors. Thus, it is essential to report and adjust for confounding factors using statistical methods.
Another limitation is that fewer included studies focused on assessing the association between structural aspects of social relationship and patients' affective symptoms. To fully understand the role of structural aspects of social relationships on patient's affective symptoms, further studies are needed that include diverse aspects of social relationships are needed.
Lastly, we found that most included studies RCTs design. To better understand the influence of social relationships on patients' affective symptoms, studies with observational longitudinal studies are needed. Additionally, most patients included this study were White, which could impede generalizability of the study findings. Therefore, a large and heterogeneous sample is needed for future studies to be representative of all women breast cancer patients from all ethnicities.

Conclusions
This scoping review summarized current evidence concerning social relationships that are associated with affective symptoms of a breast cancer patient. Of the identified social relationships, social support was most identified, followed by social constraints, family functioning, quality of relationships, social networks, and social integration. Our review results support the concept of an association between social relationships and affective symptoms of breast cancer patients, although the specific nature of this association remains unclear. Understanding different aspects of social relationships and their differential effects on patients' affective symptoms will contribute to development of interventions for best practices to support the wellbeing of this patient population.
Supporting information S1